Review Article
What is mood? A computational perspective
- James E Clark, Stuart Watson, Karl J Friston
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- Published online by Cambridge University Press:
- 26 February 2018, pp. 2277-2284
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The neurobiological understanding of mood, and by extension mood disorders, remains elusive despite decades of research implicating several neuromodulator systems. This review considers a new approach based on existing theories of functional brain organisation. The free energy principle (a.k.a. active inference), and its instantiation in the Bayesian brain, offers a complete and simple formulation of mood. It has been proposed that emotions reflect the precision of – or certainty about – the predicted sensorimotor/interoceptive consequences of action. By extending this reasoning, in a hierarchical setting, we suggest mood states act as (hyper) priors over uncertainty (i.e. emotions). Here, we consider the same computational pathology in the proprioceptive and interoceptive (behavioural and autonomic) domain in order to furnish an explanation for mood disorders. This formulation reconciles several strands of research at multiple levels of enquiry.
The prevalence of depression in general hospital inpatients: a systematic review and meta-analysis of interview-based studies
- Jane Walker, Katy Burke, Marta Wanat, Rebecca Fisher, Josephine Fielding, Amy Mulick, Stephen Puntis, Joseph Sharpe, Michelle Degli Esposti, Eli Harriss, Chris Frost, Michael Sharpe
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- 26 March 2018, pp. 2285-2298
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Background
Comorbid depression in the medically ill is clinically important. Admission to a general hospital offers an opportunity to identify and initiate treatment for depression. However, we first need to know how common depression is in general hospital inpatients. We aimed to address this question by systematically reviewing the relevant literature.
MethodsWe reviewed published prevalence studies in any language which had used diagnostic interviews of general hospital inpatients and met basic methodological quality criteria. We focussed on interview-based studies in order to estimate the proportion of patients with a diagnosis of depressive illness.
ResultsOf 158 relevant articles, 65 (41%) describing 60 separate studies met our inclusion criteria. The 31 studies that focussed on general medical and surgical inpatients reported prevalence estimates ranging from 5% to 34%. There was substantial, highly statistically significant, heterogeneity between studies which was not materially explained by the covariates we were able to consider. The average of the reported prevalences was 12% (95% CI 10–15), with a 95% prediction interval of 4–32%. The remaining 29 studies, of a variety of specific clinical populations, are described.
ConclusionsThe available evidence suggests a likely prevalence high enough to make it worthwhile screening hospital inpatients for depression and initiating treatment where appropriate. Further, higher quality, research is needed to clarify the prevalence of depression in specific settings and to further explore the reasons for the observed heterogeneity in estimates.
Interpersonal processes in paranoia: a systematic review
- Susanne F. Meisel, Philippa A. Garety, Daniel Stahl, Lucia R. Valmaggia
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- 20 March 2018, pp. 2299-2312
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Paranoid ideation is a core feature of psychosis, and models of paranoia have long proposed that it arises in the context of disturbances in the perception of the self. However, to develop targeted interventions, there is a benefit in clarifying further, which aspects of self-perception are implicated. Interpersonal sensitivity is a personality trait which has been associated with the risk of paranoid thinking in the general population. However, not all studies have found this link. We aimed to review the empirical literature assessing the association between interpersonal sensitivity and paranoia in both general population and clinical samples; and to explore if associations found differed depending on whether state or trait paranoia was assessed. The review followed PRISMA guidelines. Articles were identified through a literature search in OVID (PsychINFO, MEDLINE) and Web of Science up to December 2016. Fourteen studies with a total of 12 138 participants were included. All studies were of ‘fair’ or ‘good’ quality. A robust association was found between interpersonal sensitivity and paranoia in clinical and general population samples alike, regardless of the method of assessment of both paranoia and interpersonal sensitivity. Although this finding was more pronounced in studies of trait paranoia, it is likely that differences in study purpose, measurement, and power explain these differences. Findings from this review support the hypothesis that feelings of personal vulnerability and exaggerated socially evaluative concerns are central for both onset and maintenance of paranoid symptoms, suggesting avenues for future research in targeted interventions.
Original Articles
Neural correlates of ostracism in transgender persons living according to their gender identity: a potential risk marker for psychopathology?
- Sven C. Mueller, Katrien Wierckx, Sara Boccadoro, Guy T'Sjoen
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- 15 January 2018, pp. 2313-2320
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Background
Stigmatization in society carries a high risk for development of psychopathology. Transgender persons are at particularly high risk for such stigmatization and social rejection by others. However, the neural correlates of ostracism in this group have not been captured.
MethodTwenty transgender men (TM, female-to-male) and 19 transgender women (TW, male-to-female) already living in their gender identity and 20 cisgender men (CM) and 20 cisgender women (CW) completed a cyberball task assessing both exclusion and re-inclusion during functional magnetic resonance imaging (fMRI).
ResultsDuring psychosocial stress between-group differences were found in the dorsal and ventral anterior cingulate cortex (ACC) and the inferior frontal gyrus (IFG). Patterns were consistent with sex assigned at birth, i.e. CW showed greater activation in dorsal ACC and IFG relative to CM and TW. During re-inclusion, transgender persons showed greater ventral ACC activity relative to CW, possibly indicating persistent feelings of exclusion. Functional connectivity analyses supported these findings but showed a particularly altered functional connectivity between ACC and lateral prefrontal cortex in TM, which may suggest reduced emotional regulation to the ostracism experience in this group. Depressive symptoms or hormonal levels were not associated with these findings.
ConclusionThe results bear implications for the role of social exclusion in development of mental health problems in socially marginalized groups.
Sibling bullying in middle childhood and psychotic disorder at 18 years: a prospective cohort study
- Slava Dantchev, Stanley Zammit, Dieter Wolke
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- 12 February 2018, pp. 2321-2328
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Background
Being bullied by a sibling has been recently identified as a potential risk factor for developing depression and self-harm. It is unknown whether this risk extends to other serious mental health problems such as psychosis. We investigated whether sibling bullying victimization or perpetration in middle childhood was prospectively associated with psychotic disorder in early adulthood.
MethodsThe current study investigated 6988 participants of the Avon Longitudinal Study of Parents and Children, a UK community-based birth cohort. Sibling bullying was reported at 12 years and psychotic disorder was assessed via a semi-structured interview at 18 years.
ResultsInvolvement in sibling bullying was associated with psychotic disorder in a dose-response fashion, even after controlling for a range of confounders. Those involved several times a week were 2–3 times more likely to meet criteria for a psychotic disorder [odds ratio (OR); 95% confidence interval (CI)]: victimization (OR 2.74; CI 1.28–5.87); perpetration (OR 3.16; CI 1.35–7.41). Categorical analysis indicated that particularly victims (OR 3.10; CI 1.48–6.50) and bully-victims (OR 2.66; CI 1.24–5.69) were at increased risk of psychotic disorder. Involvement in both sibling and peer bullying had a dose-effect relationship with a psychotic disorder, with those victimized in both contexts having more than four times the odds for a psychotic disorder (OR 4.57; CI 1.73–12.07).
ConclusionParents and health professionals should be aware of the adverse long-term effects of sibling bullying.
Hormone therapy, gender affirmation surgery, and their association with recent suicidal ideation and depression symptoms in transgender veterans
- Raymond P. Tucker, Rylan J. Testa, Tracy L. Simpson, Jillian C. Shipherd, John R. Blosnich, Keren Lehavot
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- 14 January 2018, pp. 2329-2336
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Background
Access to transition-related medical interventions (TRMIs) for transgender veterans has been the subject of substantial public interest and debate. To better inform these important conversations, the current study investigated whether undergoing hormone or surgical transition intervention(s) relates to the frequency of recent suicidal ideation (SI) and symptoms of depression in transgender veterans.
MethodsThis study included a cross-sectional, national sample of 206 self-identified transgender veterans. They self-reported basic demographics, TRMI history, recent SI, and symptoms of depression through an online survey.
ResultsSignificantly lower levels of SI experienced in the past year and 2-weeks were seen in veterans with a history of both hormone intervention and surgery on both the chest and genitals in comparison with those who endorsed a history of no medical intervention, history of hormone therapy but no surgical intervention, and those with a history of hormone therapy and surgery on either (but not both) the chest or genitals when controlling for sample demographics (e.g., gender identity and annual income). Indirect effect analyses indicated that lower depressive symptoms experienced in the last 2-weeks mediated the relationship between the history of surgery on both chest and genitals and SI in the last 2-weeks.
ConclusionsResults indicate the potential protective effect that TRMI may have on symptoms of depression and SI in transgender veterans, particularly when both genitals and chest are affirmed with one's gender identity. Implications for policymakers, providers, and researchers are discussed.
An ecological momentary assessment evaluation of emotion regulation abnormalities in schizophrenia
- Katherine Frost Visser, Farnaz Zamani Esfahlani, Hiroki Sayama, Gregory P. Strauss
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- 24 January 2018, pp. 2337-2345
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Background
Prior studies using self-report questionnaires and laboratory-based methods suggest that schizophrenia is characterized by abnormalities in emotion regulation (i.e. using strategies to increase or decrease the frequency, duration, or intensity of negative emotion). However, it is unclear whether these abnormalities reflect poor emotion regulation effort or adequate effort, but limited effectiveness. It is also unclear whether dysfunction results primarily from one of the three stages of the emotion regulation process: identification, selection, or implementation.
MethodThe current study used ecological momentary assessment (EMA) to address these questions in the context of everyday activities. Participants included 28 outpatients diagnosed with schizophrenia (SZ) and 28 demographically matched healthy controls (CN) who completed 6 days of EMA reports of in-the-moment emotional experience, emotion regulation strategy use, and context.
ResultsResults indicated that SZ demonstrated adequate emotion regulation effort, but poor effectiveness. Abnormalities were observed at each of the three stages of the emotion regulation process. At the identification stage, SZ initiated emotion regulation efforts at a lower threshold of negative emotion intensity. At the selection stage, SZ selected more strategies than CN and strategies attempted were less contextually appropriate. At the implementation stage, moderate to high levels of effort were ineffective at decreasing negative emotion.
ConclusionsFindings suggest that although SZ attempt to control their emotions using various strategies, often applying more effort than CN, these efforts are unsuccessful; emotion regulation abnormalities may result from difficulties at the identification, selection, and implementation stages.
Changes in cannabis potency and first-time admissions to drug treatment: a 16-year study in the Netherlands
- Tom P. Freeman, Peggy van der Pol, Wil Kuijpers, Jeroen Wisselink, Ravi K. Das, Sander Rigter, Margriet van Laar, Paul Griffiths, Wendy Swift, Raymond Niesink, Michael T. Lynskey
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- 31 January 2018, pp. 2346-2352
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Background
The number of people entering specialist drug treatment for cannabis problems has increased considerably in recent years. The reasons for this are unclear, but rising cannabis potency could be a contributing factor.
MethodsCannabis potency data were obtained from an ongoing monitoring programme in the Netherlands. We analysed concentrations of δ-9-tetrahydrocannabinol (THC) from the most popular variety of domestic herbal cannabis sold in each retail outlet (2000–2015). Mixed effects linear regression models examined time-dependent associations between THC and first-time cannabis admissions to specialist drug treatment. Candidate time lags were 0–10 years, based on normative European drug treatment data.
ResultsTHC increased from a mean (95% CI) of 8.62 (7.97–9.27) to 20.38 (19.09–21.67) from 2000 to 2004 and then decreased to 15.31 (14.24–16.38) in 2015. First-time cannabis admissions (per 100 000 inhabitants) rose from 7.08 to 26.36 from 2000 to 2010, and then decreased to 19.82 in 2015. THC was positively associated with treatment entry at lags of 0–9 years, with the strongest association at 5 years, b = 0.370 (0.317–0.424), p < 0.0001. After adjusting for age, sex and non-cannabis drug treatment admissions, these positive associations were attenuated but remained statistically significant at lags of 5–7 years and were again strongest at 5 years, b = 0.082 (0.052–0.111), p < 0.0001.
ConclusionsIn this 16-year observational study, we found positive time-dependent associations between changes in cannabis potency and first-time cannabis admissions to drug treatment. These associations are biologically plausible, but their strength after adjustment suggests that other factors are also important.
Maternal early pregnancy obesity and depressive symptoms during and after pregnancy
- Satu M. Kumpulainen, Polina Girchenko, Marius Lahti-Pulkkinen, Rebecca M. Reynolds, Soile Tuovinen, Anu-Katriina Pesonen, Kati Heinonen, Eero Kajantie, Pia M. Villa, Esa Hämäläinen, Hannele Laivuori, Katri Räikkönen
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- 17 January 2018, pp. 2353-2363
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Background
Previous studies have linked maternal obesity with depressive symptoms during and after pregnancy. It remains unknown whether obesity associates with consistently elevated depressive symptoms throughout pregnancy, predicts symptoms postpartum when accounting for antenatal symptoms, and if co-morbid hypertensive and diabetic disorders add to these associations. We addressed these questions in a sample of Finnish women whom we followed during and after pregnancy.
MethodsEarly pregnancy body mass index, derived from the Finnish Medical Birth Register and hospital records in 3234 PREDO study participants, was categorized into underweight (<18.5 kg/m2), normal weight (18.5–24.99 kg/m2), overweight (25–29.99 kg/m2), and obese (⩾30 kg/m2) groups. The women completed the Center for Epidemiological Studies Depression Scale biweekly during pregnancy, and at 2.4 (s.d. = 1.2) and/or 28.2 (s.d. = 4.2) weeks after pregnancy.
ResultsIn comparison to normal weight women, overweight, and obese women reported higher levels of depressive symptoms and had higher odds of clinically significant depressive symptoms during (23% and 43%, respectively) and after pregnancy (22% and 36%, respectively). Underweight women had 68% higher odds of clinically significant depressive symptoms after pregnancy. Overweight and obesity also predicted higher depressive symptoms after pregnancy in women not reporting clinically relevant symptomatology during pregnancy. Hypertensive and diabetic disorders did not explain or add to these associations.
ConclusionsMaternal early pregnancy overweight and obesity and depressive symptoms during and after pregnancy are associated. Mental health promotion should be included as an integral part of lifestyle interventions in early pregnancy obesity and extended to benefit also overweight and underweight women.
Respiration pattern variability and related default mode network connectivity are altered in remitted depression
- Vera Eva Zamoscik, Stephanie Nicole Lyn Schmidt, Martin Fungisai Gerchen, Christos Samsouris, Christina Timm, Christine Kuehner, Peter Kirsch
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- 16 January 2018, pp. 2364-2374
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Background
Studies with healthy participants and patients with respiratory diseases suggest a relation between respiration and mood. The aim of the present analyses was to investigate whether emotionally challenged remitted depressed participants show higher respiration pattern variability (RPV) and whether this is related to mood, clinical outcome and increased default mode network connectivity.
MethodsTo challenge participants, sad mood was induced with keywords of personal negative life events in individuals with remitted depression [recurrent major depressive disorder (rMDD), n = 30] and matched healthy controls (HCs, n = 30) during functional magnetic resonance imaging. Respiration was measured by means of a built-in respiration belt. Additionally, questionnaires, a daily life assessment of mood and a 3 years follow-up were applied. For replication, we analysed RPV in an independent sample of 53 rMDD who underwent the same fMRI paradigm.
ResultsDuring sad mood, rMDD compared with HC showed greater RPV, with higher variability in pause duration and respiration frequency and lower expiration to inspiration ratio. Higher RPV was related to lower daily life mood and predicted higher depression scores as well as relapses during a 3-year follow-up period. Furthermore, in rMDD compared with HC higher main respiration frequency exhibited a more positive association with connectivity of the posterior cingulate cortex and the right parahippocampal gyrus.
ConclusionsThe results suggest a relation between RPV, mood and depression on the behavioural and neural level. Based on our findings, we propose interventions focusing on respiration to be a promising additional tool in the treatment of depression.
Cortical morphology development in patients with 22q11.2 deletion syndrome at ultra-high risk of psychosis
- Maria Carmela Padula, Marie Schaer, Marco Armando, Corrado Sandini, Daniela Zöller, Elisa Scariati, Maude Schneider, Stephan Eliez
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- 17 January 2018, pp. 2375-2383
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Background
Patients with 22q11.2 deletion syndrome (22q11DS) present a high risk of developing psychosis. While clinical and cognitive predictors for the conversion towards a full-blown psychotic disorder are well defined and largely used in practice, neural biomarkers do not yet exist. However, a number of investigations indicated an association between abnormalities in cortical morphology and higher symptoms severities in patients with 22q11DS. Nevertheless, few studies included homogeneous groups of patients differing in their psychotic symptoms profile.
MethodsIn this study, we included 22 patients meeting the criteria for an ultra-high-risk (UHR) psychotic state and 22 age-, gender- and IQ-matched non-UHR patients. Measures of cortical morphology, including cortical thickness, volume, surface area and gyrification, were compared between the two groups using mass-univariate and multivariate comparisons. Furthermore, the development of these measures was tested in the two groups using a mixed-model approach.
ResultsOur results showed differences in cortical volume and surface area in UHR patients compared with non-UHR. In particular, we found a positive association between surface area and the rate of change of global functioning, suggesting that higher surface area is predictive of improved functioning with age. We also observed accelerated cortical thinning during adolescence in UHR patients with 22q11DS.
ConclusionsThese results, although preliminary, suggest that alterations in cortical volume and surface area as well as altered development of cortical thickness may be associated to a greater probability to develop psychosis in 22q11DS.
Neuropsychiatric symptoms and cognitive profile in mild cognitive impairment with Lewy bodies
- Paul C Donaghy, John-Paul Taylor, John T O'Brien, Nicola Barnett, Kirsty Olsen, Sean J Colloby, Jim Lloyd, George Petrides, Ian G McKeith, Alan J Thomas
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- 24 January 2018, pp. 2384-2390
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Background
The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD).
MethodsParticipants were ⩾60 years old with MCI. Each had a thorough clinical and neuropsychological assessment and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or more diagnostic features of dementia with Lewy bodies were present (visual hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic criteria: non-visual hallucinations, delusions, anxiety, depression and apathy.
ResultsMCI-LB (n = 41) had a higher LBNSSC than MCI-AD (n = 24; 1.8 ± 1.1 v. 0.7 ± 0.9, p = 0.001). 67% of MCI-LB had two or more of those symptoms, compared with 16% of MCI-AD (Likelihood ratio = 4.2, p < 0.001). MCI-LB subjects scored lower on tests of attention, visuospatial function and verbal fluency. However, cognitive test scores alone did not accurately differentiate MCI-LB from MCI-AD.
ConclusionsMCI-LB is associated with neuropsychiatric symptoms and a cognitive profile similar to established DLB. This supports the concept of identifying MCI-LB based on the presence of core diagnostic features of DLB and abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric clinical features identified in the 2017 DLB diagnostic criteria was helpful in differentiating between MCI-LB and MCI-AD.
Effects of cumulative illness severity on hippocampal gray matter volume in major depression: a voxel-based morphometry study
- Dario Zaremba, Verena Enneking, Susanne Meinert, Katharina Förster, Christian Bürger, Katharina Dohm, Dominik Grotegerd, Ronny Redlich, Bruno Dietsche, Axel Krug, Tilo Kircher, Harald Kugel, Walter Heindel, Bernhard T Baune, Volker Arolt, Udo Dannlowski
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- 08 February 2018, pp. 2391-2398
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Background
Patients with major depression show reduced hippocampal volume compared to healthy controls. However, the contribution of patients’ cumulative illness severity to hippocampal volume has rarely been investigated. It was the aim of our study to find a composite score of cumulative illness severity that is associated with hippocampal volume in depression.
MethodsWe estimated hippocampal gray matter volume using 3-tesla brain magnetic resonance imaging in 213 inpatients with acute major depression according to DSM-IV criteria (employing the SCID interview) and 213 healthy controls. Patients’ cumulative illness severity was ascertained by six clinical variables via structured clinical interviews. A principal component analysis was conducted to identify components reflecting cumulative illness severity. Regression analyses and a voxel-based morphometry approach were used to investigate the influence of patients’ individual component scores on hippocampal volume.
ResultsPrincipal component analysis yielded two main components of cumulative illness severity: Hospitalization and Duration of Illness. While the component Hospitalization incorporated information from the intensity of inpatient treatment, the component Duration of Illness was based on the duration and frequency of illness episodes. We could demonstrate a significant inverse association of patients’ Hospitalization component scores with bilateral hippocampal gray matter volume. This relationship was not found for Duration of Illness component scores.
ConclusionsVariables associated with patients’ history of psychiatric hospitalization seem to be accurate predictors of hippocampal volume in major depression and reliable estimators of patients’ cumulative illness severity. Future studies should pay attention to these measures when investigating hippocampal volume changes in major depression.
Brain–behavior patterns define a dimensional biotype in medication-naïve adults with attention-deficit hyperactivity disorder
- Hsiang-Yuan Lin, Luca Cocchi, Andrew Zalesky, Jinglei Lv, Alistair Perry, Wen-Yih Isaac Tseng, Prantik Kundu, Michael Breakspear, Susan Shur-Fen Gau
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- Published online by Cambridge University Press:
- 07 February 2018, pp. 2399-2408
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Background
Childhood-onset attention-deficit hyperactivity disorder (ADHD) in adults is clinically heterogeneous and commonly presents with different patterns of cognitive deficits. It is unclear if this clinical heterogeneity expresses a dimensional or categorical difference in ADHD.
MethodsWe first studied differences in functional connectivity in multi-echo resting-state functional magnetic resonance imaging (rs-fMRI) acquired from 80 medication-naïve adults with ADHD and 123 matched healthy controls. We then used canonical correlation analysis (CCA) to identify latent relationships between symptoms and patterns of altered functional connectivity (dimensional biotype) in patients. Clustering methods were implemented to test if the individual associations between resting-state brain connectivity and symptoms reflected a non-overlapping categorical biotype.
ResultsAdults with ADHD showed stronger functional connectivity compared to healthy controls, predominantly between the default-mode, cingulo-opercular and subcortical networks. CCA identified a single mode of brain–symptom co-variation, corresponding to an ADHD dimensional biotype. This dimensional biotype is characterized by a unique combination of altered connectivity correlating with symptoms of hyperactivity-impulsivity, inattention, and intelligence. Clustering analyses did not support the existence of distinct categorical biotypes of adult ADHD.
ConclusionsOverall, our data advance a novel finding that the reduced functional segregation between default-mode and cognitive control networks supports a clinically important dimensional biotype of childhood-onset adult ADHD. Despite the heterogeneity of its presentation, our work suggests that childhood-onset adult ADHD is a single disorder characterized by dimensional brain–symptom mediators.
Dynamic networks of PTSD symptoms during conflict
- Talya Greene, Marc Gelkopf, Sacha Epskamp, Eiko Fried
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- 28 February 2018, pp. 2409-2417
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Background
Conceptualizing posttraumatic stress disorder (PTSD) symptoms as a dynamic system of causal elements could provide valuable insights into the way that PTSD develops and is maintained in traumatized individuals. We present the first study to apply a multilevel network model to produce an exploratory empirical conceptualization of dynamic networks of PTSD symptoms, using data collected during a period of conflict.
MethodsIntensive longitudinal assessment data were collected during the Israel–Gaza War in July–August 2014. The final sample (n = 96) comprised a general population sample of Israeli adult civilians exposed to rocket fire. Participants completed twice-daily reports of PTSD symptoms via smartphone for 30 days. We used a multilevel vector auto-regression model to produce contemporaneous and temporal networks, and a partial correlation network model to obtain a between-subjects network.
ResultsMultilevel network analysis found strong positive contemporaneous associations between hypervigilance and startle response, avoidance of thoughts and avoidance of reminders, and between flashbacks and emotional reactivity. The temporal network indicated the central role of startle response as a predictor of future PTSD symptomatology, together with restricted affect, blame, negative emotions, and avoidance of thoughts. There were some notable differences between the temporal and contemporaneous networks, including the presence of a number of negative associations, particularly from blame. The between-person network indicated flashbacks and emotional reactivity to be the most central symptoms.
ConclusionsThis study suggests various symptoms that could potentially be driving the development of PTSD. We discuss clinical implications such as identifying particular symptoms as targets for interventions.
Differential neural reward mechanisms in treatment-responsive and treatment-resistant schizophrenia
- Lucy D. Vanes, Elias Mouchlianitis, Tracy Collier, Bruno B. Averbeck, Sukhi S. Shergill
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- Published online by Cambridge University Press:
- 14 February 2018, pp. 2418-2427
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Background
The significant proportion of schizophrenia patients refractory to treatment, primarily directed at the dopamine system, suggests that multiple mechanisms may underlie psychotic symptoms. Reinforcement learning tasks have been employed in schizophrenia to assess dopaminergic functioning and reward processing, but these have not directly compared groups of treatment-refractory and non-refractory patients.
MethodsIn the current functional magnetic resonance imaging study, 21 patients with treatment-resistant schizophrenia (TRS), 21 patients with non-treatment-resistant schizophrenia (NTR), and 24 healthy controls (HC) performed a probabilistic reinforcement learning task, utilizing emotionally valenced face stimuli which elicit a social bias toward happy faces. Behavior was characterized with a reinforcement learning model. Trial-wise reward prediction error (RPE)-related neural activation and the differential impact of emotional bias on these reward signals were compared between groups.
ResultsPatients showed impaired reinforcement learning relative to controls, while all groups demonstrated an emotional bias favoring happy faces. The pattern of RPE signaling was similar in the HC and TRS groups, whereas NTR patients showed significant attenuation of RPE-related activation in striatal, thalamic, precentral, parietal, and cerebellar regions. TRS patients, but not NTR patients, showed a positive relationship between emotional bias and RPE signal during negative feedback in bilateral thalamus and caudate.
ConclusionTRS can be dissociated from NTR on the basis of a different neural mechanism underlying reinforcement learning. The data support the hypothesis that a favorable response to antipsychotic treatment is contingent on dopaminergic dysfunction, characterized by aberrant RPE signaling, whereas treatment resistance may be characterized by an abnormality of a non-dopaminergic mechanism – a glutamatergic mechanism would be a possible candidate.
Shifts in positive and negative psychotic symptoms and anger: effects on violence
- Jeremy W. Coid, Constantinos Kallis, Mike Doyle, Jenny Shaw, Simone Ullrich
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- Published online by Cambridge University Press:
- 27 February 2018, pp. 2428-2438
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Background
Changes in positive and negative symptom profiles during acute psychotic episodes may be key drivers in the pathway to violence. Acute episodes are often preceded by fluctuations in affect before psychotic symptoms appear and affective symptoms may play a more important role in the pathway than previously recognised.
MethodsWe carried out a prospective cohort study of 409 male and female patients discharged from medium secure services in England and Wales to the community. Measures were taken at baseline (pre-discharge), 6 and 12 months post-discharge using the Positive and Negative Syndrome Scale. Information on violence was obtained using the McArthur Community Violence Instrument and Police National Computer.
ResultsThe larger the shift in positive symptoms the more likely violence occurred in each 6-month period. However, shifts in angry affect were the main driving factor for positive symptom shifts associated with violence. Shifts in negative symptoms co-occurred with positive and conveyed protective effects, but these were overcome by co-occurring shifts in anger. Severe but stable delusions were independently associated with violence.
ConclusionsIntensification of angry affect during acute episodes of psychosis indicates the need for interventions to prevent violence and is a key driver of associated positive symptoms in the pathway to violence. Protective effects against violence exerted by negative symptoms are not clinically observable during symptom shifts because they are overcome by co-occurring anger.
Symptoms of persistent complex bereavement disorder, depression, and PTSD in a conjugally bereaved sample: a network analysis
- Matteo Malgaroli, Fiona Maccallum, George A. Bonanno
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- Published online by Cambridge University Press:
- 18 July 2018, pp. 2439-2448
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Background
Complicated and persistent grief reactions afflict approximately 10% of bereaved individuals and are associated with severe disruptions of functioning. These maladaptive patterns were defined in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as persistent complex bereavement disorder (PCBD), but its criteria remain debated. The condition has been studied using network analysis, showing potential for an improved understanding of PCBD. However, previous studies were limited to self-report and primarily originated from a single archival dataset. To overcome these limitations, we collected structured clinical interview data from a community sample of newly conjugally bereaved individuals (N = 305).
MethodsGaussian graphical models (GGM) were estimated from PCBD symptoms diagnosed at 3, 14, and 25 months after the loss. A directed acyclic graph (DAG) was generated from initial PCBD symptoms, and comorbidity networks with DSM-5 symptoms of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) were analyzed 1 year post-loss.
ResultsIn the GGM, symptoms from the social/identity PCBD symptoms cluster (i.e. role confusion, meaninglessness, and loneliness) tended to be central in the network at all assessments. In the DAG, yearning activated a cascade of PCBD symptoms, suggesting how symptoms lead into psychopathological configurations. In the comorbidity networks, PCBD and depressive symptoms formed separate communities, while PTSD symptoms divided in heterogeneous clusters.
ConclusionsThe network approach offered insights regarding the core symptoms of PCBD and the role of persistent yearnings. Findings are discussed regarding both clinical and theoretical implications that will serve as a step toward a more integrated understanding of PCBD.
Correspondence
A co-twin control study of the association between combat exposure, PTSD and obesity in male veterans
- K. S. Mitchell, E. J. Wolf, M. J. Lyons, J. Goldberg, K. M. Magruder
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- Published online by Cambridge University Press:
- 18 June 2018, pp. 2449-2452
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Front Cover (OFC, IFC) and matter
PSM volume 48 issue 14 Cover and Front matter
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- Published online by Cambridge University Press:
- 07 September 2018, pp. f1-f2
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